The objective of this work is to identify and characterize the genetic changes (somatic and constitutional) and other deranged mechanisms (such as those involving growth factors, their receptors signal transduction, or viral infection) leading to the pathogenesis of lung cancer and to use this information to develop new methods to prevent, diagnose and treat this disease. This work has uncovered abnormalities in the dominant and recessive oncogenes ("tumor suppressor" genes). The dominant oncogenes include those of the myc and ras family, and a complex role for those of the jun family. The recessive oncogenes include several genes in chromosome region 3p, 11p, the rb gene on 13q 14, the p53 gene on 17p13 as well as multiple other areas. We have also begun a search for an HIV like retrovirus in the pathogenesis of lung cancer with analogy to the putative retrovirus causing ovine pulmonary carcinomatosis. Growth factor and receptor work has demonstrated the presence of receptors for opioid peptides and nicotine on all classes of lung cancer cells as well as endogenous production of opioids leading to an hypothesis about their role as negative growth regulators, and the role of nicotine in reversing this effect.